Faculty Collaboration Database

Nicotinic acetylcholine receptor expression and regulation in the rat kidney after ischemia-reperfusion injury. Am J Physiol Renal Physiol 2008 Sep;295(3):F654-61

Date

07/11/2008

Pubmed ID

18614620

Pubmed Central ID

PMC2536882

DOI

10.1152/ajprenal.90255.2008

Scopus ID

2-s2.0-54449088798 (requires institutional sign-in at Scopus site)   59 Citations

Abstract

The cholinergic anti-inflammatory pathway is a mechanism whereby local inflammation is modulated by the brain via the vagus nerve and nicotinic acetylcholine receptors (nAChRs). The nAChR family are ligand-gated ion channels that consist of many different subtypes formed by the specific assembly of five polypeptide subunits including alpha1-10, beta1-4, gamma, delta, and epsilon. The alpha7 receptor (alpha7nAChR) mediates the anti-inflammatory effects of cholinergic stimulation. We recently demonstrated that cholinergic agonists attenuate renal ischemia-reperfusion (I/R) injury in rats. We also showed that tubular epithelial cells express functional nAChRs in vitro. The current studies report the expression, localization, and regulation of the alpha7nAChR in the rat kidney after I/R injury. We also examined, in this model, potential interactions between cholinergic stimulation and the STAT3 pathway, a key signaling cascade that has been linked to alpha7nAChR activation. RT-PCR and immunohistochemistry showed constitutive expression of many nAChR subunits. Immunohistochemistry localized basal alpha7nAChR expression to the endothelium of cortical peritubular capillaries, and its distribution was upregulated after I/R injury. Western blotting also showed an increase in alpha7nAChR subunit protein after renal I/R injury. Interestingly, pretreatment with nicotine, which improves the outcome after renal I/R injury, reduced the alpha7nAChR protein after I/R injury. Finally, we found that I/R injury stimulated the STAT3 pathway, whereas pretreatment with nicotine downregulated its activation. These results suggest that the alpha7nAChR plays an important role in the pathophysiology of renal I/R injury.

Author List

Yeboah MM, Xue X, Javdan M, Susin M, Metz CN

MESH terms used to index this publication - Major topics in bold

Animals
Cholinergic Agonists
Immunohistochemistry
Kidney
Male
Nicotine
Proteasome Endopeptidase Complex
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic
Reperfusion Injury
STAT3 Transcription Factor
alpha7 Nicotinic Acetylcholine Receptor